Anti-Thymocyte Globulin, Cyclosporine, and RAD in Islet Transplantation (NITA)

Inclusion Criteria: Primary islet allotransplant Patients with type 1 diabetes mellitus under intensive insulin management Age 18 or older Ability to give written informed consent Exclusion Criteria: Age less than 18 years. BMI >26 kg/m2. Insulin requirement of > 50 IU per day. Positive C-peptide response to intravenous arginine stimulation. Untreated proliferative retinopathy. Creatinine clearance < 60 ml/min/1.73 m2 for females and 70 ml/min/1.73 m2 for males. Serum creatinine >1.3 mg/dl for females, >1.5 mg/dl for males. Previous pancreas or islet transplant. Presence of history of panel-reactive anti-HLA antibodies >10%. Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures. Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB). Negative screen for Epstein-Barr Virus (EBV). Invasive aspergillus infection within year prior to study entry. History of malignancy. Active alcohol or substance abuse History of non-adherence to prescribed regimens. Psychiatric disorder making the subject not a suitable candidate for transplantation. Inability to provide informed consent. Baseline Hgb < 11.7 g/dl in females, or < 13 g/dl in males; lymphopenia (<1,000/microL), or leukopenia (<3,000 total leukocytes/microL), or an absolute CD4+ count <500/microL., or platelets <150,000/microL History of coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or patient with INR >1.5. Severe co-existing cardiac disease. Baseline liver function tests outside of normal range or history of significant liver disease. Active peptic ulcer disease. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications. Presence of severe allergy requiring acute or chronic treatment, or hypersensitivity to drugs similar to RAD (e.g., macrolides). Known hypersensitivity to rabbit proteins. Hyperlipidemia (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl). Addison's disease. Under treatment requiring chronic use of systemic steroids. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.